NAD(+) in COVID-19 and viral infections

NAD(+), as an emerging regulator of immune responses during viral infections, may be a promising therapeutic target for coronavirus disease 2019 (COVID-19). In this Opinion, we suggest that interventions that boost NAD(+) levels might promote antiviral defense and suppress uncontrolled inflammation. We discuss the association between low NAD(+) concentrations and risk factors for poor COVID-19 outcomes, including aging and common comorbidities. Mechanistically, we outline how viral infections can further deplete NAD(+) and its roles in antiviral defense and inflammation. We also describe how coronaviruses can subvert NAD(+)-mediated actions via genes that remove NAD(+) modifications and activate the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Finally, we explore ongoing approaches to boost NAD(+) concentrations in the clinic to putatively increase antiviral responses while curtailing hyperinflammation.